Adenovirus-Mediated Overexpression of REIC/Dkk-3 Selectively Induces Apoptosis in Human Prostate Cancer Cells through Activation of c-Jun-NH sub(2)-Kinase

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 21; pp. 9617 - 9622
• Main Authors: Abarzua, Fernando, Sakaguchi, Masakiyo, Takaishi, Mikiro, Nasu, Yasutomo, Kurose, Kyouhei, Ebara, Shin, Miyazaki, Masahiro, Namba, Masayoshi, Kumon, Hiromi, Huh, Nam-ho
• Format: Journal Article
• Language: English
• Published: 01-11-2005
• Subjects: Adenovirus
• ISSN: 0008-5472

Alteration in genes which takes place during malignant conversion and progression could be potential targets for gene therapy. We previously identified REIC/Dkk-3 as a gene whose expression is reduced in many human cancers. Here, we showed that expression of REIC/Dkk-3 was consistently reduced in human prostate cancer tissues in a stage-dependent manner. Forced expression of REIC/Dkk-3 induced apoptosis in human prostate cancer cell lines lacking endogenous REIC/Dkk-3 expression but not in REIC/Dkk-3-proficient normal prostate epithelial and stromal cells. The apoptosis involved c-Jun-NH sub(2)-kinase activation, mitochondrial translocation of Bax, and reduction of Bcl-2. A single injection of an adenovirus vector carrying REIC/Dkk-3 showed a dramatic antitumor effect on a xenotransplanted human prostate cancer. Thus, REIC/Dkk-3 could be a novel target for gene-based therapy of prostate cancer.